Transcriptome analysis of AAV-induced retinopathy models expressing human VEGF, TNF-α and IL-6 in murine eyes
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE200191 | GEO | 2022/11/11
REPOSITORIES: GEO
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Project description:Retinopathies are multifactorial diseases with complex pathologies that eventually lead to vision loss. Animal models facilitate the understanding of the pathophysiology and identification of novel treatment options. However, each animal model reflects only specific disease aspects and understanding of the specific molecular changes in most disease models is limited. Here, we conducted transcriptome analysis of murine ocular tissue transduced with recombinant Adeno-associated viruses (AAVs) expressing either human VEGF-A, TNF-α, or IL-6. VEGF expression led to a distinct regulation of extracellular matrix (ECM)-associated genes. In contrast, both TNF-α and IL-6 led to more comparable gene expression changes in interleukin signaling, and the complement cascade, with TNF-α-induced changes being more pronounced. Furthermore, integration of single cell RNA-Sequencing data suggested an increase of endothelial cell-specific marker genes by VEGF, while TNF-α expression increased the expression T-cell markers. Both TNF-α and IL-6 expression led to an increase in macrophage markers. Finally, transcriptomic changes in AAV-VEGF treated mice largely overlapped with gene expression changes observed in the oxygen-induced retinopathy model, especially regarding ECM components and endothelial cell-specific gene expression. Altogether, our study represents a valuable investigation of gene expression changes induced by VEGF, TNF-α, and IL-6 and will aid researchers in selecting appropriate animal models for retinopathies based on their agreement with the human pathophysiology.
| S-EPMC9653384 | biostudies-literature
Project description:To characterize underlying changes in the retinal pigment epithelium (RPE)/choroid with age, we produced gene expression profiles for the RPE/choroid and compared the transcriptional profiles of the RPE/choroid from young and old mice. The changes in the aged RPE/choroid suggest that the tissue has become immunologically active. Such phenotypic changes in the normal aged RPE/choroid may provide a background for the development of age-related macular degeneration. Experiment Overall Design: We compared the gene expression of retinal pigmental epithelium/choroid from young and old animals. There were 4 samples from young mice and 4 samples from old mice. Each sample contained 4 retinal pigmental epithelium/choroid from 2 animals
2008-06-11 | E-GEOD-10965 | biostudies-arrayexpress
Project description:Single-cell Transcriptomes of RPE-specific AAV-GFP/AAV-PDGF-D mouse RPE-choroid complex
| PRJNA794114 | ENA
Project description:To characterize underlying changes in the retinal pigment epithelium (RPE)/choroid with age, we produced gene expression profiles for the RPE/choroid and compared the transcriptional profiles of the RPE/choroid from young and old mice. The changes in the aged RPE/choroid suggest that the tissue has become immunologically active. Such phenotypic changes in the normal aged RPE/choroid may provide a background for the development of age-related macular degeneration. Keywords: age-related change
2008-03-29 | GSE10965 | GEO
Project description:The iris is a fine structure that controls the amount of light that enters the eye. The ciliary body controls the shape of the lens and produces aqueous humor. The retinal pigment epithelium and choroid (RPE/choroid) are essential in supporting the retina and absorbing light energy that enters the eye. Proteins were extracted from iris, ciliary body, and RPE/choroid tissues of eyes from five individuals and fractionated using SDS-PAGE. After in-gel digestion, peptides were analyzed using LC-MS/MS on an Orbitrap Elite mass spectrometer. In iris, ciliary body, and RPE/choroid, we identified 2,959, 2,867, and 2,755 non-redundant proteins with protein false positive rate <1%. There were 43 unambiguous protein isoforms identified in iris, ciliary body, and RPE/choroid. Four “missing proteins” were found in ciliary body. The MS proteome database of the human iris, ciliary body, and RPE/choroid may serve as a valuable resource for future investigations of the eye in health and disease. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD001424.
2016-02-04 | PXD002194 | Pride
Project description:Transcriptome analysis of AAV-induced retinopathy models expressing human VEGF, TNF-α and IL-6 in murine eyes
| PRJNA823648 | ENA
Project description:The ciliary body (CB) of the human eye consists of the non-pigmented (NPE) and pigmented (PE) neuro-epithelia. We investigated the gene expression of the NPE and PE, to shed light on the molecular mechanisms underlying the most important functions of the CB. Therefore we isolated NPE and PE cells from seven healthy human donor eyes using laser dissection microscopy. Next, we performed RNA isolation, amplification, labeling and hybridization against 44k Agilent microarrays. We performed the microarrays against a common reference sample, namely human RPE/choroid RNA. We performed 7 replicates of PE samples from 7 different donors and 7 NPE replicates from the same 7 different donors.
2012-09-18 | E-GEOD-37957 | biostudies-arrayexpress
Project description:<p>Proper spatial differentiation of retinal cell types is necessary for normal human vision. Many retinal diseases, such as Best disease and male germ cell associated kinase (MAK)-associated retinitis pigmentosa, preferentially affect distinct topographic regions of the retina. While much is known about the distribution of cell types in the retina, the distribution of molecular components across the posterior pole of the eye has not been well-studied. To investigate regional difference in molecular composition of ocular tissues, we assessed differential gene expression across the temporal, macular, and nasal retina and retinal pigment epithelium (RPE)/choroid of human eyes using RNA-Seq. RNA from temporal, macular, and nasal retina and RPE/choroid from four human donor eyes was extracted, poly-A selected, fragmented, and sequenced as 100 bp read pairs. Digital read files were mapped to the human genome and analyzed for differential expression using the Tuxedo software suite. Retina and RPE/choroid samples were clearly distinguishable at the transcriptome level. Numerous transcription factors were differentially expressed between regions of the retina and RPE/choroid. Photoreceptor-specific genes were enriched in the peripheral samples, while ganglion cell and amacrine cell genes were enriched in the macula. Within the RPE/choroid, RPE-specific genes were upregulated at the periphery while endothelium associated genes were upregulated in the macula. Consistent with previous studies, BEST1 expression was lower in macular than extramacular regions. The MAK gene was expressed at lower levels in macula than in extramacular regions, but did not exhibit a significant difference between nasal and temporal retina. The regional molecular distinction is greatest between macula and periphery and decreases between different peripheral regions within a tissue. Datasets such as these can be used to prioritize candidate genes for possible involvement in retinal diseases with regional phenotypes. </p> <p>Reprinted from <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=25446321">Whitmore, S.S., Wagner, A.H., DeLuca, A.P., Drack, A.V., Stone, E.M., Tucker, B.A., Zeng, S., Braun, T.A., Mullins, R.F., Scheetz, T.E., 2014. Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq. Experimental Eye Research</a>. Used under <a href="http://creativecommons.org/licenses/by-nc-sa/3.0/">Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported </a>license.</p> <p>Additional RNA sequencing was performed on temporal, macular, nasal, inferior, and superior retina from a fifth subject and is included in this dataset. See original publication for details.</p>
| phs001151 | dbGaP
Project description:PURPOSE To identify retinal pigment epithelial (RPE)/choroid genes and their relevant expression pathways affected by intravitreal injections of dexamethasone and triamcinolone acetonide in mice at clinically relevant time points for patient care. METHODS Differential gene expression of over 34,000 well-characterized mouse genes, in the RPE/choroid of 6 week old C57BL/6J mice were analyzed after intravitreal steroid injections at 1 week and 1 month post injection, using Affymetrix Mouse Genome 430 2.0 microarrays. The data were analyzed using GeneSpringGX12.5 and Ingenuity Pathway Analysis (IPA) microarray analysis software for biologically relevant changes. RESULTS Both triamcinolone and dexamethasone caused differential activation of genes involved in âCircadian Rhythm Signalingâ pathway at both time points tested. Triamcinolone (TAA) uniquely induced significant changes in gene expression in âCalcium Signalingâ (1 week) and âGlutamate Signalingâ pathways (1month). In contrast, Dexamethasone (Dex) affected the âGABA Receptor Signalingâ (1 week) and âSerotonin Receptor Signalingâ (1month) pathways. CONCLUSIONS Understanding how intraocular steroids affect the gene expression of RPE/choroid is clinically relevant. This in vivo study has elucidated several genes and pathways that are potentially altering the circadian rhythms and several other neurotransmitter pathways in RPE/choroid cells during intravitreal steroid injections, which likely has consequences in the dysregulation of RPE function and neurodegeneration of the retina. Total of 18 RPE/choroid samples were analysed. There were two time points, day7 and day30. Each time point had three groups: BSS control, DEX treatment and TAA treatment. Each group had three biological replicas.
2016-08-01 | E-GEOD-49872 | biostudies-arrayexpress
Project description:The iris is a fine structure that controls the amount of light that enters the eye. The ciliary body controls the shape of the lens and produces aqueous humor. The retinal pigment epithelium and choroid (RPE/choroid) are essential in supporting the retina and absorbing light energy that enters the eye. Proteins were extracted from iris, ciliary body, and RPE/choroid tissues of eyes from five individuals and fractionated using SDS-PAGE. After in-gel digestion, peptides were analyzed using LC-MS/MS on an Orbitrap Elite mass spectrometer. In iris, ciliary body, and RPE/choroid, we identified 2,959, 2,867, and 2,755 non-redundant proteins with protein false positive rate <1%. There were 43 unambiguous protein isoforms identified in iris, ciliary body, and RPE/choroid. Four “missing proteins” were found in ciliary body. The MS proteome database of the human iris, ciliary body, and RPE/choroid may serve as a valuable resource for future investigations of the eye in health and disease. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD001424.
2017-11-29 | MSV000081766 | MassIVE